The Animal Models Core will assist the overall program project by providing service for the generation, maintenance, and analysis of genetically modified mouse models. In addition, the core will provide tissue samples for histological and biochemical analysis, and will generate epithelial cell lines and primary cultures from the animal models for in-vitro analysis. The core component is highly integrative, being utilized by all four of the research projects for provision of cells and tissues for analysis, and for three of the four projects for the production and maintenance of novel mouse models (Project 1, 3, 4), Several existing mouse models will be employed, including Nox-1 knockout mice, which have been generated previously by Project 4 (Lambeth) in conjunction with the Director of Core B (Martin), and mitochondria! thioredoxin transgenic mice (TRX2) previously generated here at Emory in collaboration between Dr. Martin, and Dr. Dean Jones (letter of collaboration attached). Additional existing strains to be utilized in this program include, but may not be limited to, Villin k-rasv12 Tg, APC 1638, and ARC min mice. The core facility will also produce and characterize a novel transgenic model, villin-MTH-1 for Project 4 (Grouse). This is especially significant, since this lab has no previous animal models experience, and would not be able to generate and analyze these mice without the expertise of the core component. The core will maintain and genotype the colony, and provide real-time colony data access to all program participants through a comercially available relational database (Scion, Topaz Technologies) which is currently in use by the Core Directors laboratory. In addition to the live animal models, the core will also provide transformed cell lines to the program participants for biochemical analysis. This will be critical to several of the projects, and will allow for strong linkage between the mamallian models and the yeast system. By provision of these services, the Animal Models Core will contribute significantly to the overall goals of the program project from a scientific perspective. In addition, the inclusion of these services into a comprehensive core component will provide additional benefit to the project as a whole, through consolidation of effort, avoidance of unnecessary experimental duplication and by drawing upon the collective expertise of the core personnel.